U.S. patent number 5,126,937 [Application Number 07/626,413] was granted by the patent office on 1992-06-30 for biological information measurement apparatus.
This patent grant is currently assigned to Terumo Kabushiki Kaisha. Invention is credited to Norio Daikuhara, Takeshi Shimomura, Naoto Uchida, Norihiko Ushizawa, Shuichiro Yamaguchi.
United States Patent |
5,126,937 |
Yamaguchi , et al. |
June 30, 1992 |
Biological information measurement apparatus
Abstract
A biological information measurement apparatus is adapted to
measure biological information in an extracorporeal circuration or
in a living body by various measurement circuits comprising circuit
elements which are not affected by electrical disturbances, and to
transmit the results of measurement in the form of a non-electrical
signal which is not affected by electrical disturbances. Measured
values from measurement sections are gathered at a central
processing section separated from the measurement sections. The
processing section converts the measured values into output values,
compensates the values for temperature and outputs the values to a
display unit and recorder.
Inventors: |
Yamaguchi; Shuichiro (Fuji,
JP), Ushizawa; Norihiko (Fujinomiya, JP),
Daikuhara; Norio (Fujinomiya, JP), Shimomura;
Takeshi (Fujinomiya, JP), Uchida; Naoto
(Fujinomiya, JP) |
Assignee: |
Terumo Kabushiki Kaisha (Tokyo,
JP)
|
Family
ID: |
27303548 |
Appl.
No.: |
07/626,413 |
Filed: |
December 14, 1990 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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382053 |
Jul 13, 1989 |
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68245 |
Jun 30, 1987 |
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Foreign Application Priority Data
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Jul 1, 1986 [JP] |
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61-152744 |
Oct 22, 1986 [JP] |
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61-249473 |
Apr 3, 1987 [JP] |
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62-81276 |
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Current U.S.
Class: |
600/301; 600/322;
600/326; 374/173; 422/82.02; 422/82.03; 422/82.01; 422/82.04 |
Current CPC
Class: |
A61B
5/145 (20130101); G01N 33/492 (20130101); A61B
5/14539 (20130101) |
Current International
Class: |
A61B
5/00 (20060101); G01N 33/487 (20060101); G06F
015/00 (); A61B 005/05 () |
Field of
Search: |
;364/413.11,413.03
;128/631,635 ;374/172 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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21172 |
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May 1984 |
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AU |
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0171927 |
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Feb 1986 |
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EP |
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55-129900 |
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Oct 1980 |
|
JP |
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56-109645 |
|
Aug 1981 |
|
JP |
|
61-288834 |
|
Dec 1986 |
|
JP |
|
WO81/01505 |
|
Jun 1981 |
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WO |
|
86/01919 |
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Mar 1986 |
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WO |
|
Primary Examiner: Shaw; Dale M.
Assistant Examiner: Chung; Xuong M.
Attorney, Agent or Firm: Burns, Doane, Swecker &
Mathis
Parent Case Text
This application is a continuation of application Ser. No. 382,053,
filed Jul. 13, 1989, abandoned, which is a continuation of
application Ser No. 068,245, filed Jun. 30, 1987, abandoned.
Claims
What is claimed is:
1. A biological information measurement apparatus comprising:
biological information measuring means for continuously measuring
electrical values corresponding to a plurality of biological
information including at least one of ion-concentration and
gas-concentration in body fluid and for outputting biological
information signals;
first temperature measuring means in a body with said measuring
means for measuring the temperature of the body fluid adjacent said
biological information measuring means and for outputting a first
temperature information signal;
transmitting means for non-electrically transmitting the biological
information signals and the first temperature information signal by
a time sharing method wherein it is possible to discriminate
between said plurality of biological information and the first
temperature information;
converting means for converting the biological information signals
and the first temperature information signal transmitted by said
transmitting means into an electrical signals;
correcting means for correcting parameters used in a calibration
equation which determines said parameters through measuring said
electrical values measured by said biological information measuring
means under plural kinds of fluids having known ion-concentration
or gas-concentration and known temperature, wherein the number of
said plural kinds of fluids corresponds to the number of said
parameters, each time before starting continuous measurement;
analysis means for analyzing the biological information signals,
which have been converted into the electrical signals by said
converting means, in dependence upon the type of biological
information, with compensation of the measured biological
information including temperature-compensation by using the first
temperature information signal and with said corrected parameters,
which has been converted into an electrical signal by said
converting means; and
output means for outputting analytical results from said analyzing
means to an external unit, the analytical results being
standardized to correspond to the type of biological
information.
2. The apparatus according to claim 1, wherein said transmitting
means comprises optical communication means having one optical
fiber cables.
3. The apparatus according to clam 1, wherein said output means
comprises display means.
4. The apparatus according to claim 1, wherein said measuring means
includes an internal power supply.
5. The apparatus according to claim 1, wherein said measuring means
includes a differential amplifier as means for measuring
electromotive force, said amplifier having a high input
resistance.
6. The apparatus according to claim 1, further comprising second
temperature measuring means for measuring the temperature of said
biological information measuring means and for outputting a second
temperature information signal in order to temperature-compensate
said biological information measuring means.
7. The apparatus according to claim 1, further comprising
temperature computing means for computing a temperature through a
convergency technique by using process loop from said first
temperature information signal which has been converted into the
electrical signal by said converting means, said analysis means
analyzes the biological information signal with
temperature-compensation by using said computed temperature.
8. The apparatus according to claim 1, wherein said transmitting
means comprises optical communication means having a plurality of
optical fiber cables.
9. The apparatus according to claim 1, wherein said output means
comprises memory means.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to an apparatus for measuring biological
information. More particularly, the invention relates to a
biological measurement apparatus used to sensing and monitoring a
specimen in an extracorporeal circuration, or to perform sensing
and monitoring in vivo.
2. Description of the Prior Art
In clinical and medical fields, the continuous measurement and
monitoring of ion concentration, gas concentration and the
concentration of biological substances, especially enzymes, is
desirable. Though an appreciation of continuous monitoring is
growing in general medical treatment, a practical continuous
monitoring system has not yet been realized. There are various
reasons for this. One is that ion sensors and sensors for
identifying biological substances do not operate stably in a living
body or in biological solutions. Another is that ion sensors, gas
sensors and enzyme sensors, which typically are glass electrodes,
generally have a high impedence which renders them susceptible to
adverse electrical effects. As a result, satisfactory monitoring
circuits are not available. Moreover, when monitoring is performed
over an extended period of time, variations of temperature affect
measurement precision, thus making it difficult to achieve highly
precise monitoring. Furthermore, owing to the influence of
electrical disturbances, there is a limit upon how far apart the
measurement section and processing section of the system can be
separated from each other.
SUMMARY OF THE INVENTION
An object of the present invention is to provide a biological
information measurement apparatus for measuring such biological
information as the concentration of a specimen in an extracorporeal
circulation using biological living body fluids and biological
solutions, and in a fluidic solution.
Another object of the present invention is to provide a biological
information measurement apparatus in which measured values are
temperature-compensated in response to temperature variations in
living body fluids, biological solutions and measuring devices.
Still another object of the present invention is to provide a
biological information measurement apparatus in which a measurement
section and processing section are separated via transmission means
not susceptible to the influence of electrical disturbances,
whereby the measurement section can be made easy to handle and
remote centralized supervision performed by the processing section
can be facilitated.
A further object of the present invention is to provide a
biological information measurement apparatus in which sensor output
(current, electromotive force, resistance, etc.) can be measured
stably and very accurately.
The present inventors have already proposed ion sensors, gas
sensors and enzyme sensors suitable for continuous monitoring and
have succeeded in fabricating the aforementioned biological
information measurement apparatus as the result of exhaustive
research relating to continuous measurement systems suitable for
use in the medical field for stable, highly precise measurement of
ion concentration, gas concentration and the like.
According to the present invention, the foregoing objects are
attained by providing a biological information measurement
apparatus comprising measuring means for measuring biological
information continuously, transmitting means for non-electrically
transmitting a biological information signal outputted by the
measuring means, converting means for converting the biological
information signal transmitted by the transmitting means into an
electrical signal, analyzing means for analyzing the biological
information signal, which has been converted into the electrical
signal by the converting means, in dependence upon the type of
biological information, and output means for outputting analytical
results from the analyzing means to an external unit, the
analytical results being made to correspond to the type of
biological information.
In a preferred embodiment of the invention, the transmitting means
comprises optical communication means having one or a plurality of
optical fiber cables.
In a preferred embodiment of the invention, the output means
comprises display means or memory means.
In a preferred embodiment of the invention, the measuring means
includes an internal power supply.
In a preferred embodiment of the invention, the measuring means
includes a differential amplifier as means for measuring
electromotive force, the amplifier having an input resistance of at
least 10.sup.11 .OMEGA..
In a preferred embodiment of the invention, the measuring means
includes temperature measuring means for measuring the temperature
of a biological information measuring section in order to
temperature-compensate the biological information measuring
section.
In a preferred embodiment of the invention, the measuring means
includes temperature measuring means for measuring the temperature
of a living body in order to temperature-compensate the measured
biological information.
Thus, the invention makes it possible to provide a biological
information measurement apparatus for measuring such biological
information as the concentration of a specimen in an extracorporeal
circulation using biological living body fluids and biological
solutions, and in a fluidic solution.
Further, it is possible to provide a biological information
measurement apparatus in which measured values are
temperature-compensated in response to temperature fluctuations in
living body fluids, biological solutions and measuring devices.
Further, it is possible to provide a biological information
measurement apparatus in which a measurement section and processing
section are separated via transmission means not susceptible to the
influence of electrical disturbances, whereby the measurement
section can be made easy to handle and remote centralized
supervision performed by the processing section can be
facilitated.
Moreover, it is possible to provide a biological information
measurement apparatus in which sensor output (current,
electromotive force, resistance, etc.) can be measured stably and
very accurately.
Other features and advantages of the present invention will be
apparent from the following description taken in conjunction with
the accompanying drawings, in which like reference characters
designate the same or similar parts throughout the figures
thereof.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1(a), (b) are block diagrams illustrating an embodiment of a
biological information measurement apparatus according to the
invention;
FIGS. 2(a)-(d) are more detailed block diagrams illustrating the
embodiment of the biological information measurement apparatus
according to the invention;
FIG. 3 is circuit diagram of a high-input resistance differential
amplifier for an ion sensor;
FIG. 4 is a circuit diagram of a circuit for measuring
temperature;
FIG. 5 is a circuit diagram of a polarographic microcurrent
measuring circuit;
FIG. 6(a)-(c) are views showing the general features of the
embodiment of the biological information measurement apparatus;
FIGS. 7(a)-(e) are flow charts of a control program executed by a
processing unit;
FIGS. 8(a), (b) are flow charts illustrating a control program of
an interface;
FIGS. 9(a), (b) are flow charts of a program for measured
temperature calculation;
FIG. 10 is graph illustrating the results of measurement comprising
temperature values and temperature-compensated pH values obtained
with the biological information measurement apparatus of the
embodiment;
FIGS. 11(a)-(c) are graphs illustrating the results of measurement
comprising temperature values, electrical potential values and
temperature-compensated CO.sub.2 partial pressure values (i.e.
pCO.sub.2 values) obtained with the biological information
measurement apparatus of the embodiment;
FIGS. 12(a)-(c) are graphs illustrating the results of measurement
comprising temperature values, electrical potential values and
temperature-compensated CO.sub.2 partial pressure values (i.e.
pCO.sub.2 values) obtained with the biological information
measurement apparatus of the embodiment for a case where a
circulating liquid flowrate is varied;
FIGS. 13(a), (b) are flow charts of a program for calculating the
partial pressure of carbon dioxide;
FIG. 14 is a flow chart of a program for calculating the partial
pressure of oxygen;
FIG. 15 is a schematic view of a circulating circuit using an
experiment; and
FIGS. 16(a)-(c) are views illustrating the results of measurement
obtained in an experiment.
DESCRIPTION OF THE PREFERRED EMBODIMENT
A preferred embodiment of the present invention will now be
described in detail in accordance with the accompanying
drawings.
FIGS. 1(a), (b) are block diagrams illustrating an embodiment of a
biological information measurement apparatus according to the
invention. The apparatus comprises an input unit 1, an interface 2
and a processing unit 3. The input unit 1 and interface 2 are
interconnected by optical fiber cables 4, and the interface 2 and
processing unit 3 are connected by an electrical cable 5. The
results of processing executed by the processing unit 3 are
outputted to a display unit 6 and recorder 7.
Conventionally, the input unit 1 and interface 2 are integrated and
an output section for the measurement data is isolated by a
photocoupler or the like. If the input unit 1 has a high
input-impedence, however, further isolation is required. In the
illustrated embodiment, the input unit 1 is reduced in size, a
primary or secondary battery is used and the output signal is
converted into a optical signal which is then transmitted by the
optical fiber cables 4. This assures a high degree of isolation. As
a result, the superposition of noise entering through ground
circuitry and the power supply can be reduced to make highly
precise measurement possible. This also facilitates remote
measurement and monitoring.
The input unit 1 measures one or more sensor outputs, such as
electromotive force, current and resistance value. After the
measured value, which is an analog quantity, is converted into a
digital value, the resulting digital value is converted into an
optical signal transmitted, through the optical cables 4, to the
interface in the form of measurement data. If only one optical
cable is used for transmitting the data, the outputs from a
plurality of sensors can be transferred by a time-sharing method. A
plurality of optical cables can be used if desired.
In an embodiment of the input unit 1, the input unit comprises a
high-input resistance voltmeter for measuring the electromotive
force of an ion sensor, and a circuit for measuring the output
(resistance) of a temperature sensor for internally compensating
the ion sensor and of a temperature sensor for measuring
temperature in a solution.
FIGS. 2(a)-(d) are more detailed block diagrams showing the
biological information measurement apparatus of the illustrated
embodiment.
An input unit 1a is for measuring ion, gas and enzyme concentration
and is adapted to simultaneously perform a temperature measurement
for internal temperature compensation. To this end, the input unit
1a comprises a high-input resistance voltmeter 10 for measuring
emf, thermometers 11, 12 for internal temperature measurement and
solution temperature measurement, respectively, AD converters 13,
14, 15 for converting the outputs of the voltmeter 10 and
thermometers 11, 12 into digital values, a multiplexer 16 for
selecting the digital values resulting from the conversion, and an
optical transmission circuit 17 for converting the digital values
into optical signals and transmitting the optical signals to the
interface 2.
FIG. 3 illustrates an example of a high-input resistance
differential amplifier for an ion sensor, which amplifier is used
as a high-input resistance voltmeter for measuring emf. The
high-input resistance voltmeter 10 comploys a high-input impedence
(no less than 10.sup.11 .OMEGA.), low-drift (less than 2
.mu.V/C.sup.0) differential amplifier constituted by a readily
available operational amplifier (e.g. the OPA111BM, manufactured by
Burr-Brown Co. or the TLC-27L2 manufactured by Texas Instruments).
The AD converters 13, 14, 15 are double integrating-type,
41/2-digit AD converters (the ICL7135CPI, manufactured by Intersil
Inc.). The multiplexer 16 and digital circuitry are constituted by
a CMOS logic IC in order to reduce power consumption. The AD
converters 13, 14, 15 are started simultaneously e.g. every 400 ms
and perform a serial conversion, with header characters being
assigned to their respective output values.
FIG. 4 shows and examples of a temperature measuring circuit. The
thermometers 11 and 12 each include a readily available operational
amplifier to construct a highly accurate constant-current source.
Preferably, the constant-current source is set to no more than 70
.mu.A, with a current range of 10 .mu.A-50 .mu.A being especially
preferred. A circuit in which the amount of power consumed by a
temperature sensor element (thermister) is less than 50 .mu.W may
be provided as the constant-current source. Preferably, the circuit
should be designed so that the amount of power consumed by a
temperature sensor element (thermister) is 20 .mu.W. The voltage
that results when this constant current flows through the
temperature sensor element (thermister) is measured by the analog
to digital (AD) converter 14, or 15. During calibration of the
apparatus, a signal indicative of the fact is generated by a switch
27. This signal is delivered to the interface 2 by the multiplexer
16.
In order for the biological information measurement apparatus of
the embodiment to measure biological information continuously with
a high accuracy, it is required that temperature measurement and
temperature compensation based on this measurement be performed
quickly and accurately. In particular, it is required that
temperature be measured with an accuracy of within 0.01.degree. C.
Accordingly, in order to measure temperature in the illustrated
embodiment, a thermister is used and not a thermocouple or platinum
resistor requiring a high-performance device. Further, in view of
the fact that the thermister is inserted into a living body, use is
made of a miniature thermister inserted into an insulative tube. In
order to reduce an error due to self-heating, the value of the
constant current that flows through the thermister is set to 50
.mu.A in the illustrated embodiment.
In a conventional thermister thermometer of simple type, the
thermometer includes a linearizing circuit obtained by connecting a
fixed resistor in series with the thermister element. Since
temperature is measured with such an arrangement, accuracy is
limited to .+-.0.5 C.degree.. This can be understood from the
following equation for calculating temperature T (.degree.K) from
the resistance value R (chm) of a thermister:
where R.sub.0 (chm) represents the resistance value at the
temperature TO(.degree.K). Further, B is a function of temperature,
though this can be regarded as a constant in a narrow temperature
range (e.g..+-.2.degree. C.). For this reason, highly precise
measurements cannot be taken with the aforementioned linearizing
circuit in a broad temperature range (e.g. 0-50.degree. C.). By
using the temperature T.sub.0, B is expressed as follows in a range
T.sub.1 (.degree.K):
where X=ln(T/T.sub.0)/1/(T.sub.0 -1/T)
In the above, B.sub.0, C, X.sub.0, E and F are constants and
represent physical values related to the composition of the
thermister.
In the illustrated embodiment, the resistance values from the
thermisters are converted into digital values by the AD converters
14, 15 and an AD converter 21 and the digital values are
transmitted to the processing unit 3 via the optical fiber cables
4, interface 2 and cable 5. On the basis of these values, the
processing unit 3 calculates temperature rapidly and accurately in
accordance with an arithmetic program, described below.
The input unit 1b is adapted to measure the concentration of
O.sub.2 by measuring the polarographic current of O.sub.2, by way
of example, and includes a microammeter 18, a thermometer 19 for
temperature measurement, AD converters 20, 21, a multiplexer 22 and
an optical transmission circuit 23. The microammeter 18 comprises a
-0.5 V .about.-0.7 V constant-voltage source, and a circuit for
converting a microcurrent of 10.sup.-6 .about.10.sup.-11 A into a
voltage. FIG. 5 illustrates an example of a polarographic
microcurrent measuring circuit.
The AD converters 20, 21 are double integrating-type, 41/2-digit AD
converters (the ICL7135CPI, manufactured by Intersil Inc.). The
multiplexer 22 and digital circuitry are constituted by a CMOS
logic IC in order to reduce power consumption. The AD converters
20, 21 are started simultaneously e.g. every 400 ms and perform a
serial conversion, with header characters being assigned to their
respective output values.
The thermometer 19 includes a readily available operational
amplifier to construct a highly accurate constant-current source.
Preferably, the constant-current source is set to no more than 70
.mu.A, with a current range of 10 .mu.A-50 .mu.A being especially
preferred. The voltage that results when this constant current
flows through the temperature sensor element (thermister) is
measured by the AD converter 21. During calibration of the
apparatus, a signal indicative of the fact is generated by a switch
28. This signal is delivered to the interface 2 by the multiplexer
22.
The interface 2 includes an optical reception circuit 24 having a
plurality (e.g. five in the illustrated embodiment)) of input
channels for converting optical signals from the input unit 1 into
electric signals, a multiplexer 25 for selecting a channel of
signal data, and an Input/Output (I/0) interface 26 for
transmitting the signal data selected by the multiplexer 25 to the
processor 3. The latter converts the signal data into concentration
units before outputting the data to the display unit 6 and recorder
7.
The signal data are not only outputted to the memory unit 6 and
recorder 7 but are also stored in a memory device so that they may
be read out whenever required. Though the measurement data received
from the input unit 1 may be delivered directly to the processing
unit 3, the burden on the processing unit 3 can be reduced if the
interface 2 is provided with a Random Access Memory (RAM) 320 and
the measurement data are arranged and temporarily stored in the RAM
320 in accordance with a program stored in a ROM 321. The
multiplexer 25 uses an eight-bit Central Processing Unit (CPU) to
convert the received data into character and numerical value codes,
stores these channel by channel and transfers the data in response
to a data request from the I/0 interface 26. The I/0 interface 26
uses an IEEE-488 bus interface, but a general-purpose RS-232C or
the like can also be used.
The central processing unit 3 comprises a CPU 331, a ROM 332 for
storing a processing program, and an auxiliary RAM 333 and converts
the signal from the interface 2 into units of ion concentration or
gas partial pressure (concentration) by performing a calculation in
accordance with a calibration curve prepared in advance. The
processing unit 3 is also capable of compensating for a temperature
fluctuation in a sensor by using sensor temperature. A personal
computer having an eight-bit CPU or 16-bit CPU can be utilized as
the processing unit 3. By assembling the interface 2 on a board,
the interface can be inserted into the expansion slot of a personal
computer.
FIGS. 6(a)-(c) are views showing the general features of the
embodiment of the biological information measurement apparatus,
FIGS. 7(a)-(e) are flow charts of a control program executed by the
processing unit 3 and stored in the ROM 332, and FIGS. 8(a), (b)
are flow charts illustrating the control program of the interface
2. This control program is stored in the ROM 321.
In FIGS. 7(a)-(e), the system is initialized at a step S71. Next,
at a step S72, an interrupt demanding transmission of the
measurement data is applied to the interface 2. The program then
proceeds to a step S73, where the system waits for the measurement
data to arrive from the interface 2.
Meanwhile, the interface 2 receives the measurement data from the
input unit 1 while scanning these data in accordance with the
procedure of FIG. 8(a). Specifically, at a step S101, the interface
2 waits for the arrival of the measurement data from the input unit
1. Then, at a step S102, a different storage address is set
depending upon the connection position of the input unit 1. This is
followed by a step S103, at which measurement data are stored in a
storage area of RAM 320 that depends upon the input unit 1.
Execution of the steps S101 through S103 is repeated to store the
measurement data while all of the input units 1 are scanned in
order. Though storage addresses which differ depending upon the
connection positions are set to distinguish the differences in
biological data measured, it is also permissible to adopt an
arrangement in which measurement data from the input units 1 are
provided with identification codes for identifying the type of
biological data. This will have the advantage of raising the degree
of freedom of control since the types of biological information can
be identified without taking the connection positions into
consideration.
If there is an interrupt from the processing unit 3 calling for the
transmission of measurement data, processing is executed through
the procedure shown in FIG. 8(b). First, the measurement data
stored at the step S103 of the ordinary procedure [FIG. 8(a)] are
read out at a step S104, and the data are transmitted to the
processing unit 3 at a step S105. Next, it is determined at a step
S106 whether the transmission of all measurement data has ended. If
the answer at this step is NO, then the program returns to the step
S104 and steps S104 through S106 are repeated.
At a step S74 in FIGS. 7(a)-(e), the processing unit 3 receives the
measurement data transmitted through the steps S104 through S106
and stores the data in the RAM 333. Next, analysis that differs
depending on the type of stored measurement data is performed at
steps S75 and S84. The invention will be described for a typical
case in which the system includes an ion sensor and gas sensor.
Processing would be performed through a similar procedure for
biological information from other sensors as well.
In the case of the ion sensor, the program proceeds from the step
S75 to a step S76, where the temperature which prevails at the time
of ion measurement is calculated from temperature measurement data
obtained from the input unit corresponding to the ion sensor. A
step S77 calls for a determination as to whether pH is to be
measured. If the answer is YES, then the pH value is calculated
from the measurement data at a step S78, the pH value is corrected
at a step S79 based on the temperature calculated at the step S76,
and the corrected pH value is stored at a step S80. If the decision
rendered at the step S77 is that pH is not to be measured, then the
concentration of another ion is calculated, compensated for
temperature and stored through steps S81 through S83.
In the case of the gas sensor, the program proceeds from the step
S84 to a step S85, where the temperature which prevails at the time
of measurement performed by the gas sensor is calculated from
temperature measurement data obtained from the input unit
corresponding to the gas sensor. Gas concentration is calculated,
compensated for temperature and stored at steps S86 through
S88.
A step S89 calls for the stored results of the various measurements
to be arranged in accordance with the output formats of the display
unit 6 and recorder 7. These results are outputted to the display
unit 6 and recorder 7 at a step S90. Next, it is determined at a
step S100 whether measurement has ended. If the answer is NO, the
steps S71 through S100 are repeated to output the results of
measurement obtained next. It should be noted that multifarious
control is possible, such as outputting predetermined biological
information if it exceeds an allowable value, even if the results
of measurement are outputted at a fixed timing.
FIGS. 9(a), (b) illustrate flow charts for the calculation of
measured temperatures (also known as the convergency technique)
performed at the steps S76, S85. In FIGS. 9(a), (b), m represents
the value of a count recorded by a counter, and 1 represents the
number of times a calculation is repeated for reasons of
accuracy.
At a step S91, m is set to 0 as an initial value, l is set to a
predetermined number, and constants T.sub.0, T.sub.1, B.sub.0,
R.sub.0, X.sub.0 C, E and F are set. Next, at a step S92, the
stored thermister resistance value R received from the interface 2
together with the other measured values at the step S74 is read.
This is followed by a step S93, at which T is calculated on the
basis of R using the following equation:
Next, X is calculated on the basis of T, obtained at the step S93,
in accordance with the following equation:
Then, on the basis of T calculated at the step S93 and X calculated
at the step S94, B is calculated from the following equation at a
step S95:
The program then proceeds to a step S96, at which T is calculated
anew based on T calculated at the step S93 and B calculated at the
step S95. Next, m is incremented at a step S97, and it is checked
at a step S98 whether m is equal to or greater than the initially
set l. If the answer is no, the program returns to the step S94 and
steps S94 through S98 are repeated. If m is found to be equal to or
greater than l at the step S98, the program proceeds to a step S99,
at which the present values of m, T and B are stored, after which
the program returns. It should be noted that l may be a fixed
number or may be set to a number which will cause computation to be
repeated until a change due to a single calculation of the value of
T falls below a predetermined value.
EXPERIMENT 1
The thermister employed should be a miniature thermister inserted
into a polyimide tube and having an outer diameter of no more than
1.00 mm. Preberable characteristics are B.sub.0 =3244.about.3408,
R.sub.0 =7400.about.7800, C=30.7, E=-0.0766,
F=0.338.times.10.sup.-4, with the thermal time constant being no
more than 50 msec. In the present experiment, the thermister used
had an outer diameter of 0.55 mm and the characteristics B.sub.0
=3350, R.sub.0 =7793, C =30.7, E=-0.0766, F=0.338.times.10.sup.-4,
thermal time constant=50 msec. Preferably, the constant current
value is set to less than 70 .mu.A to reduce the error ascribable
to self-heating of the thermister, or a constant-current source is
used that will hold the amount of power consumed by the thermister
element to less than 20 .mu.W. In the experiment, the circuit shown
in FIG. 4 was employed so that the value of the constant current
flowing through the thermister element would be 50 .mu.A.
Temperature was measured using a thermoregulator (CTE-24WS, Yamato
Scientific Co. Ltd.) as a constant-temperature bath, and a
temperature measuring device (D632, manufactured by Takara
Thermistor Instruments Co. Ltd.) having an accuracy of
1/100.degree. C. was used for comparison purposes. The results are
shown in Table 1.
TABLE 1 ______________________________________ Number of
calculation loops This Invention (.degree.C.) D632
______________________________________ n = 0 23.7935 n = 1 24.0817
24.082.degree. C. n = 2 24.0781 n = 3 24.0781 n = 4 24.0781
______________________________________
It was found that an accuracy of 1/100.degree. C. could be obtained
by the first calculation loop. A difference of 0.002.degree. C.
from the value measured with the D632 for comparison purposes was
obtained, indicating good agreement. This means that it is possible
to measure temperature both rapidly and very precisely (measurement
time: less than 100 msec). Similar results were obtained even using
a constant-current source in which the amount of power consumed by
the thermister element was less than 20 .mu.W.
EXAMPLE 2
Temperature-compensated ion concentration measurement was performed
by simultaneously measuring ion concentration and temperature using
the apparatus shown in FIGS. 1(a), (b) and FIGS. 2(a)-(d).
The input unit 1a comprises the high-input resistance voltmeter 10
for ion concentration measurement, and the temperature measuring
circuits 11, 12, identical with those used in Experiment 1. The
outputs of the voltmeter 10 and circuits 11, 12 are converted into
digital signals delivered to the multiplexer 16 and then
transmitted as light signals by the optical transmitting circuit
17. The light signals are sent to the interface 2 on a time-sharing
basis via the optical fiber cable 4. The interface 2 inputs the
data to the processing unit 3. In the experiment, a GP-IB interface
(IEEE-488) was used as the interface 2. A personal computer
(PC-9801VM4, manufactured by Nippon Electric Co.) was used as the
processing unit 3.
With an ion-selective electrode, ion concentration [ION] and
electromotive force E are related by a Nernst equation.
Specifically, in the case of an anion, the equation is expressed as
follows:
Therefore, if the temperature T and electromotive force E can be
measured, then it is possible to perform a highly precise
measurement of ion concentration without the influence of a change
in temperature.
The continuous measurement of hydrogen ion concentration will now
be described as a specific example.
The potential difference E of a pH sensor in each of three types of
buffer solutions having a known temperature and pH was measured,
the coefficients a.sub.1, b.sub.1, c.sub.1 of the calibration
equation
(where T represents absolute temperature) were calculated, and a
calibration equation was formed. Next, the pH sensor and a
thermistor were set in a circulating standard blood serum
(Precinorm.RTM. U, Boehringer Mannheim GmbH). The potential E of
the pH sensor and the temperature T (=0+273.15) of the thermister
were read in by processing unit 3 through the input unit 1a,
multiplexer 16, optical fiber 4 and interface 2, and the pH value
of the circulating solution was calculated from Eq. (1). As shown
in FIG. 10, the results indicate that the pH value can be measured
very accurately even if the circulating solution temperature
.theta. varies. In FIG. 10, the "+" marks indicate the values
measured using a readily available pH sensor (the ABL3,
manufactured by Radiometer Copenhagen).
EXPERIMENT 3
Temperature-compensated measurement of the partial pressure of
carbon dioxide was performed by simultaneously measuring the
partial pressure of carbon dioxide and temperature using the
apparatus shown in FIGS. 1(a), (b) and FIGS. 2(a)-(d).
The input unit la comprises the high-input resistance voltmeter 10
for measurement of the partial pressure of carbon dioxide, and the
temperature measuring circuits 11, 12, identical with those used in
Experiment 1. The outputs of the voltmeter 10 and circuits 11, 12
are converted into digital signals delivered to the multiplexer 16
and then transmitted as light signals by the optical transmitting
circuit 17. The light signals are sent to the interface 2 on a
time-sharing basis via the optical fiber cable 4. The interface 2
inputs the data to the processing unit 3. In the experiment, a
GP-IB interface was used as the interface 2. A personal computer
(the NEC PC-9801VM4, manufactured by Nippon Electric Co.) was used
as the processing unit 3.
With the carbon dioxide electrode used in this example, the partial
pressure of carbon dioxide [pCO.sub.2 ] and electromotive force E
are related by the following equation:
where a.sub.2, b.sub.2 and s are undetermined coefficients, E
represents the measured electromotive force, and T stands for the
absolute temperature. Accordingly, we may rewrite the foregoing as
follows: ##EQU1## If the undetermined coefficients a.sub.2, b.sub.2
and s are calculated, the partial pressure of carbon dioxide can be
measured from a cubic equation. Accordingly, if the potential
difference E of a carbon dioxide electrode in three types of
solutions having a known temperature and partial pressure of carbon
dioxide is measured, and if the temperature T (.degree. C.) is
measured, then the partial pressure of carbon dioxide can be
obtained from the calibration equation (2).
The continuous measurement of carbon dioxide partial pressure will
now be described as a specific example.
A carbon dioxide electrode and a thermister are disposed in a
circulating solution (10 mM NaHCO.sub.3 +154 mM NaCl). The
potential E of the carbon dioxide electrode and the temperature T
of the thermister are read in by processing unit 3 through the
input unit 1a, multiplexer 16, optical fiber 4 and interface 2. The
partial pressure of carbon dioxide in the circulating solution is
calculated from Eq. (2) in accordance with a flow chart shown in
FIGS. 13(a), (b).
Coefficients a.sub.2, b.sub.2, s prevailing at the time of
calibration are input and set at a step S131. Next, the potential
difference and the resistance value from the thermister are read in
through the input unit 1a, multiplexer 16, optical fiber 4 and
interface 2 at a step S132, and these are stored at a step
S133.
A step S134 calls for calculation of temperature T in accordance
with the temperature calculation flow chart of FIG. 9(a), (b). This
is followed by a step S135, pCO.sub.2 is calculated from the
temperature T and potential difference E using Eq. (2). The results
of measurement are displayed at a step S136. It is determined at a
step S137 whether measurement is to continue. If the answer here is
YES, then the program returns to the step S132 and steps S132
through S137 are repeated.
As illustrated in FIGS. 11(a) through 11(c), the results of
measurement show that the value of the partial pressure of carbon
dioxide can be measured accurately even if the circulating solution
temperature 0 varies. The "+" marks indicate the measured values
obtained by sampling the circulating solution and using a readily
available carbon dioxide sensor (the ABL-30 manufactured by
Radiometer).
EXPERIMENT 4
A continuous measurement was taken in the same manner as in
Experiment 3 while the flowrate of the circulating solution (10 mM
NaHCo.sub.3 +154 mM NaCl) was varied from 500 ml/min to 200 ml/min.
As shown in FIGS. 12(a) through 12(c), the results of measurement
are unaffected by the electrical noise produced by the motor of a
roller pump and by variations in flowrate and temperature.
Furthermore, since optical fibers are used for the data
transmission, the influence of electrical external noise between
the input unit la and interface 2 is suppressed.
EXPERIMENT 5
Temperature-compensated measurement of the partial pressure of
oxygen was performed by simultaneously measuring the partial
pressure of oxygen and temperature using the apparatus shown in
FIGS. 1(a), (b) and FIGS. 2(a)-(d).
The input unit 1b comprises the micro-ammeter 18 for measurement of
the partial pressure of oxygen, and the temperature measuring
circuit 19. The outputs of the ammeter 18 and circuit 19 are
converted into digital signals delivered to the multiplexer 22 and
then transmitted as light signals by the optical transmitting
circuit 23. The light signals are sent to the interface 2 on a
time-sharing basis via the optical fiber cable 4. The interface 2
inputs the data to the processing unit 3. In the experiment, a
GP-IB interface was used as the interface 2. A personal computer
(PC-9801VM4, manufactured by Nippon Electric Co.) was used as the
processing unit 3. FIG. 14 is a flow chart illustrating the
calculation of oxygen partial pressure. In the pO.sub.2 sensor used
in the present embodiment, oxygen partial presure [pO.sub.2 ] and
the current value I are related by the following equation:
where T is the temperature (.degree. C.) prevailing at the time of
measurement. Accordingly, if the current value I of the pO.sub.2
sensor in four types of solutions having a known temperature and
partial pressure of oxygen is measured and the undetermined
coefficients a.sub.3, b.sub.3, c.sub.3, d.sub.3 of calibration
equation (3) are calculated, then, by measuring the temperature T
(.degree. C.) and current value I (A), the partial pressure of
oxygen can be measured very accurately without the influence of a
variation in temperature.
In the flow chart of FIG. 14, the pO.sub.2 sensor coefficients
a.sub.3, b.sub.3, c.sub.3, d.sub.3 previously stored are called at
a step S141. The temperature T (.degree. C.) prevailing at the time
of measurement and calculated from the thermister output is read
out at a step S142, and the received and stored sensor current
value I (A) is read out at a step S143. These values are
substituted into the following equation:
obtained by transforming the calibration equation (3), the value of
pO.sub.2 is calculated at a step S144, and the results of
calculation are stored or displayed at a step S145.
The coefficients in calibration equation (3) associated with the
pO.sub.2 sensor used in this example have the following values:
a.sub.3 =-248.3, b.sub.3 =-18.97, c3=-2.28.times.10.sup.-10 d.sub.3
=2.65.times.10.sup.-8
A circulating circuit which includes an artificial lung 151 is
shown in FIG. 15. The circuit has a flow cell 153 to which a
pO.sub.2 sensor and thermister are attached. The current value I of
the pO.sub.2 sensor and the temperature T of the thermister are
read into the processing unit 3 via the input unit 1b, multiplexer
22, optical fiber 4 and interface 2, and the processing unit 3
calculates the partial pressure of oxygen in the circulating fluid
using Eq. (3). Numeral 152 denotes a heat exchanger, 154 a
reservoir, and 155 a rotary pump.
The results of measurement are shown in FIGS. 16(a), 16(b) and
16(c). FIG. 16(a) illustrates a change in the value of an O.sub.2
reduction current which flows in the pO.sub.2 sensor, FIG. 16(b)
shows a change in thermister temperature, and FIG. 16(c)
illustrates a change in the value of pO.sub.2 calculated from
values shown in FIGS. 16(a) 16(b). The solid lines in FIG. 16(c)
are theoretical values of pO.sub.2 calculated from the volume
percentage of O.sub.2 in a mixed gas of N.sub.2 and O.sub.2 passed
through the artificial lung 151 and steam pressure. These results
show that using the system of the present embodiment makes it
possible sense the partial pressure of oxygen very accurately even
if both temperature and pO.sub.2 vary.
Thus, in accordance with the present embodiment as described above,
the power supply of the input unit is constituted by a battery and
is reduced in size. As a result, the apparatus does not require
much space in the operating room or at the bedside. Since optical
fiber cables are used for output, there is no danger of electric
shock. The measurement section and the processing section of the
apparatus are separated from each other, so that the input unit is
light in weight and easy to handle.
Further, since a high-input resistance differential amplifier is
used for ion, gas and enzyme sensing, stable measurements can be
taken without the influence of external noise.
Since a plurality of thermometers are incorporated in the input
unit so that temperature measurement and sensor temperature
compensation can be carried out, highly precise measurement is
performed.
Moreover, since a miniature (having a diameter of less than 1 mm)
thermister is used in the temperature measurement and temperature
compensation operations performed in the illustrated embodiment,
thermal capacity is low and response with respect to changes in
temperature is quick. In addition, since it is possible to
incorporate the thermister inside an ion sensor, gas sensor or
enzyme sensor, a highly precise compensation for temperature can be
made.
Since the thermister uses a constant-current source in which a
current of not more than 50 .mu.A flows, self-heating of the
thermister per se can be neglected. This makes possible highly
accurate measurement of resistance, namely temperature. By
subjecting the resistance value to high-speed repetitive processing
using a computer, the resistance value can be converted into
temperature rapidly and accurately even in a continuously changing
system. If the temperature is used, the ion sensor or gas sensor
can be subjected to a highly accurate temperature compensation.
Though the non-electrical transmission means is an optical
communication system in the illustrated embodiment, in principle
any means which is not influenced by electrical disturbances can be
used, such as sound. Measurement is not limited to pH and gas
concentration. Other biological substances can be measured by such
biosensors as enzyme sensors and microbe sensors.
* * * * *